TY - JOUR AU - Sun Shu-zhen AU - Cao Hong AU - Yao Na AU - Zhao Ling-ling AU - Zhu Xiao-fang AU - Ni Er-an AU - Zhu Qi AU - Zhu Wei-zhong PY - 2020 TI - β-Arrestin 2 mediates arginine vasopressin-induced IL-6 induction via the ERK 1/2 -NF-κB signal pathway in murine hearts JF - Acta Pharmacologica Sinica; Vol 41, No 2 (February 2020): Acta Pharmacologica Sinica Y2 - 2020 KW - N2 - Evidence to date suggests that β-arrestins act beyond their role as adapter proteins. Arginine vasopressin (AVP) may be a factor in inflammation and fibrosis in the pathogenesis of heart failure. In the present study we investigated the effect of AVP on inflammatory cytokine IL-6 production in murine hearts and the impact of β-arrestin 2-dependent signaling on AVP-induced IL-6 production. We found that administration of AVP (0.5 U/kg, iv) markedly increased the levels of IL-6 mRNA in rat hearts with the maximum level occurred at 6 h. In β-arrestin 2 KO mouse hearts, deletion of β-arrestin 2 decreased AVP-induced IL-6 mRNA expression. We then performed in vitro experiments in adult rat cardiac fibroblasts (ARCFs). We found that AVP (10 −9 –10 −6  M) dose-dependently increased the expression of IL-6 mRNA and protein, activation of NF-κB signaling and ERK 1/2 phosphorylation, whereas knockdown of β-arrestin 2 blocked AVP-induced IL-6 increase, NF-κB activation and ERK 1/2 phosphorylation. Pharmacological blockade of ERK 1/2 using PD98059 diminished AVP-induced NF-κB activation and IL-6 production. The selective V 1A receptor antagonist SR49059 effectively blocked AVP-induced NF-κB phosphorylation and activation as well as IL-6 expression in ARCFs. In AVP-treated mice, pre-injection of SR49059 (2 mg/kg, iv) abolished AVP-induced NF-κB activation and IL-6 production in hearts. The above results suggest that AVP induces IL-6 induction in murine hearts via the V 1A receptor-mediated β-arrestin2/ERK 1/2 /NF-κB pathway, thus reveal a novel mechanism of myocardial inflammation in heart failure involving the V 1A /β-arrestin 2/ERK 1/2 /NF-κB signaling pathway. UR - http://www.chinaphar.com/article/view/10089